3-Cyano-2,4,5-trifluorobenoxyl fluoride and intermediate products for the production thereof

ABSTRACT

The present invention relates to 3-cyano-2,4,5-trifluoro-benzoyl fluoride and to intermediates for its preparation and to the process for the preparation of 3-cyano-2,4,5-trifluoro-benzoyl fluoride, which starts from 5-fluoro-1,3-xylene (VIII); which is bichlorinated in the ring in the presence of a catalyst under ionic conditions to give 2,4-dichloro-5-fluoro-1,3-dimethylbenzene (VII). The latter is chlorinated in the side chains under free-radical conditions to give 2,4-dichloro-5-fluoro-3-dichloromethyl-1-trichloromethylbenzene (VT). The latter is hydrolysed via 2,4-dichloro-5-fluoro-3-dichloromethylbenzoic acid (V), which can be isolated if necessary, to give 2,4-dichloro-5-fluoro-3-formyl-benzoic acid (IV), the aldehyde group of which is reacted to give 2,4-dichloro-5-fluoro-3-N-hydroxyiminomethyl-benzoic acid (III), from which, with simultaneous conversion of the carboxyl group into the chlorocarbonyl group, water is eliminated using an acid chloride to give the nitrile 2,4-dichloro-3-cyano-5-fluoro-benzoyl chloride (II). Finally, the nitrile is subjected to fluorine/chlorine exchange.

[0001] The present invention relates to 3-cyano-2,4,5-trifluoro-benzoylfluoride, to a process for its preparation, and to other novelhalogenobenzene derivatives as intermediates.

[0002] 3-Cyano-2,4,5-trifluoro-benzoyl chloride can be used for thepreparation of antiinfective quinolonecarboxylic acids (cf. DE-A 1 963805 No.19 606 762.6=WO 97/31001). The preparation starts from2,4-dichloro-5-fluoro-3-cyanobenzoic acid and leads by a known method(cf. DE 3702393 A1) to 2,4-dichloro-3-cyano-5-fluoro-benzoyl chloride,which is then fluorinated. A disadvantage of this process is, inparticular, the Sandmeyer reaction, which proceeds with poorlyreproducible yield, using a molar amount of copper cyanide and anadditional three-fold excess of sodium cyanide to give2,4-dichloro-3-cyano-5-fluoro-benzoic acid. The use of such largeamounts of cyanide also harbours a considerable hazard potential whenthe reaction is carried out industrially.

[0003] The present invention relates to novel3-cyano-2,4,5-trifluoro-benzoyl fluoride of the formula (I)

[0004] The invention also relates to a process for the preparation of3-cyano-2,4,5-trifluoro-benzoyl chloride by chlorination of3-cyano-2,4,5-trifluoro-benzoyl fluoride.

[0005] In addition, the invention also relates to the use of3-cyano-2,4,5-trifluoro-benzoyl fluoride for the synthesis ofquinolones.

[0006] The invention further relates to a multistage process for thepreparation of 3-cyano-2,4,5-trifluoro-benzoyl fluoride, which startsfrom 5-fluoro-1,3-xylene (VIII), characterized in that5-fluoro-1,3-xylene (VIII) is bichlorinated in the ring in the presenceof a catalyst under ionic conditions to give2,4-dichloro-5-fluoro-1,3-dimethylbenzene (VII), which is thenchlorinated in the side chains under free-radical conditions to give2,4-dichloro-5-fluoro-3-dichloromethyl-1-trichloromethylbenzene (VI),which is hydrolysed via 2,4-dichloro-5-fluoro-3-dichloromethylbenzoicacid (V), which can be isolated if necessary, to give2,4-dichloro-5-fluoro-3-formyl-benzoic acid (IV), the aldehyde group ofwhich is reacted to give2,4-dichloro-5-fluoro-3-N-hydroxyiminomethyl-benzoic acid (III), fromwhich, with simultaneous conversion of the carboxyl group into thechlorocarbonyl group, water is eliminated using an acid chloride to givethe nitrile 2,4-dichloro-3-cyano-5-fluoro-benzoyl chloride (II), which,finally, is subjected to fluorine/chlorine exchange.

[0007] Alternatively, 2,4-dichloro-5-fluoro-3-formyl-benzoic acid (IV)can also be reacted to give 2,4-dichloro-5-fluoro-3-cyano-benzoic acid(IX), which can then be converted into the acid chloride (II).

[0008] The intermediates of the formulae (III) to (VII) are novelwithout exception and are likewise provided by the invention.

[0009] 3-Cyano-2,4,5-trifluoro-benzoyl fluoride is an intermediate,readily obtainable by the process described here, for the preparation of3-cyano-2,4,5-trifluoro-benzoyl chloride.

[0010] The process according to the invention is described in moredetail below.

[0011] The ring chlorination of commercially available5-fluoro-1,3-xylene (VIII) to give2,4-dichloro-5-fluoro-1,3-dimethylbenzene (VII) is carried out usingchlorine gas.

[0012] 2,4-Dichloro-5-fluoro-1,3-dimethylbenzene (VII) is novel.

[0013] The catalyst used is one or more Friedel-Crafts catalysts,preferably a Lewis acid, such as, for example, iron (III) chloride oraluminium chloride. For example, from 0.1 to 10 mol %, preferably from0.2 to 2 mol %, based on 5-fluoro-1,3-xylene, are used.

[0014] The reaction can be carried out at temperatures below roomtemperature or at slightly elevated temperature. Preference is given totemperatures between 0 and 40° C.

[0015] The chlorination can be carried out without a diluent or in asuitable inert diluent. Particularly suitable diluents are halogenatedhydrocarbons such as dichloro-, trichloro-, tetrachloromethane,1,2-dichloroethane or 1,2,4-trichlorobenzene. The chlorination can becarried out continuously or batchwise. In a continuous process, it iswise to proceed only to a low conversion because the chlorination doesnot take place with complete selectivity. In the batchwise procedure,chlorine is introduced in an amount up to approximately 0.8-1.1 times,preferably 0.8-0.95 times, the theoretical amount, the reaction mixtureachieving a solid consistency in the chlorination without diluent. It isalso advantageous in this connection to proceed only up to thisnot-too-high conversion because then the losses as a result ofsuperchlorination on the one hand and the space-time yield on the otherare in an optimum range.

[0016] The mixture is worked up, for example, by fractionaldistillation. It is advantageous to return recovered starting materialand monochlorinated compounds to the process.

[0017] The side-chain chlorination of2,4-dichloro-5-fluoro-1,3-dimethylbenzene (VII) to give2,4-dichloro-5-fluoro-3-dichloromethyl-1-trichloromethylbenzene (VI) ispreferably carried out without a diluent using chlorine gas.

[0018] 2,4-Dichloro-5-fluoro-3-dichloromethyl-1-trichloromethylbenzene(VI) is novel.

[0019] The conditions for the free-radical reaction are achieved byelevated temperature and optional irradiation with a light source oraddition of a customary free-radical initiator. Suitable light sourcesare incandescent lamps such as, preferably, halogen lamps or medium- orhigh-pressure mercury vapour lamps. Suitable free-radical initiatorsare, for example, benzoyl peroxide, di-tert-butyl peroxide or2,2-azobis(isobutteronitrile) (AIBN). The reaction temperature can bebetween 80 and 200° C., preferably 100 and 180° C., particularlypreferably between 120 and 170° C.

[0020] The chlorination can be carried out continuously or batchwise. Ina continuous process, it is wise to proceed only up to a low conversionbecause the chlorination does not take place with complete selectivity.In the batchwise procedure, chlorine is introduced in an amount up toapproximately 0.8-1.2 times, preferably 0.95-1.15 times the theoreticalamount, corresponding to from 40 to 75%, preferably from 65 to 75%,conversion to the desired product.

[0021] The reaction mixture can be worked up, for example, by fractionaldistillation or recrystallization from a suitable solvent such as, forexample, methanol. Preference is given to distillation. Insufficientlychlorinated compounds can be introduced again into the chlorination.

[0022] The chlorinated side chains are hydrolysed using a protic acid,optionally in the presence of water. Suitable protic acids are mineralacids such as, for example, sulphuric acid, hydrochloric acid orphosphoric acid, and organic acids such as, for example, formic acid,acetic acid or oxalic acid, and mixtures thereof and with a prolicsolvent such as, for example, water.

[0023] Depending on the type, concentration and amount of acid andreaction temperature, it is possible to carry out the hydrolysis of2,4-dichloro-5-fluoro-3-dichloromethyl-1-trichloromethylbenzene (VI) togive 2,4-dichloro-5-fluoro-3-formyl-benzoic acid (IV) in one or twosteps. Because the trichloromethyl group is hydrolysed significantlymore quickly, 2,4-dichloro-5-fluoro-3-dichloromethylbenzoic acid (V)can, if the reaction conditions are suitable, be isolated directly andconverted to (IV) in a further hydrolysis step. As far as the overallprocess of the preparation of 3-cyano-2,4,5-trifluoro-benzoyl fluorideaccording to the invention is concerned, it is advantageous to carry outthe hydrolysis in one step.

[0024] 2,4-Dichloro-5-fluoro-3-formyl-benzoic acid (IV) and2,4-dichloro-5-fluoro-3-dichloromethylbenzoic acid (V) are novel.

[0025] The amount of protic acid is unimportant. The acid, for example,is initially introduced and the molten aromatic compound (VI) or (V) isadded. Preference is given to using sufficient acid (mixture) for thereaction mixture to remain stirrable.

[0026] The temperature for the hydrolysis can be varied within a widerange depending on the desired product, acid and reaction time. Thetemperature is generally from 0 to 100° C.

[0027] The product can be isolated, for example, by precipitation withwater and removal by filtration or extraction.

[0028] The oxime (III) is prepared from2,4-dichloro-5-fluoro-3-formyl-benzoic acid (IV) by a generally knownmethod.

[0029] 2,4-Dichloro-5-fluoro-3-N-hydroxyiminomethyl-benzoic acid (III)is novel.

[0030] The reagent used is a salt of hydroxylamine such as, for example,the hydrochloride or sulphate, or also the free base.

[0031] If a salt of hydroxylamine is used, the reaction is carried outin the presence of an acid acceptor. Suitable acid acceptors arecustomary inorganic or organic bases. These include, preferably, thehydroxides, alkoxides, acetates, carbonates and hydrogen carbonates ofalkaline earth metals or alkali metals, such as, for example, thehydroxides of sodium, potassium or ammonium, sodium methoxide, sodiumethoxide, potassium tert-butoxide, the acetates of sodium, potassium,calcium or ammonium, the carbonate of sodium, potassium or ammonium, thehydrogen carbonates of sodium or potassium, and tertiary amines, such astrimethylamine, triethylamine, tributylamine, N,N-dimethylaniline,N,N-dimethyl-benzylamine, pyridine, N-methylpiperidine,N-methylmorpholine, N,N-dimethylaminopyridine, diazabicyclooctane(DABCO), diazabicyclononene (DBN) or diazabicycloundecene (DBU).

[0032] The reaction is carried out in the presence of a diluent.Suitable diluents are water, organic solvents and any mixtures thereof.Examples which may be mentioned are: ethers, such as diethyl ether,diisopropyl ether, methyl t-butyl ether, methyl t-amyl ether, dioxane,tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane, diethyleneglycol dimethyl ether or anisole; nitriles, such as acetonitrile,propionitrile, n- or i-butyronitrile; alcohols, such as methanol,ethanol, n- or i-propanol, n-, iso-, sec- or tert-butanol, ethanediol,propane-1,2-diol, ethoxyethanol, methoxyethanol, diethylene glycolmonomethyl ether, diethylene glycol monoethyl ether; water.

[0033] The temperature for the reaction can be varied within arelatively wide range. It is generally chosen to be between 10 and 100°C., preferably between 20 and 80° C.

[0034] Per mol of formylbenzoic acid (IV), from 1 to 1.5 equivalents ofhydroxylamine (salt) are used, and from 200 to 2000 ml, preferably from500 to 1000 ml, of diluent are used. Per equivalent of hydroxylamine,from 1 to 5, preferably from 1.1 to 3, equivalents of acid acceptor areused.

[0035] For work-up, the reaction mixture is acidified, for example usinga mineral acid, and, where appropriate, the product is extracted using asuitable solvent such as, for example, methyl tert-butyl ether, or thesolid is filtered off.

[0036] If the reaction of (IV) with hydroxylamine or a salt ofhydroxylamine is carried out in the presence of formic acid, then thereaction product obtained is the nitrile (IX). Preference is given tousing hydroxylamine hydrochloride.

[0037] The reaction can be carried out in the presence of a diluent.Suitable diluents are water, organic solvents and any mixtures thereof.Preferably, the reaction is carried out in from 85% to 98% strengthaqueous formic acid.

[0038] The temperature of the reaction can be varied in a relativelywide range. It is generally chosen to be between 10 and 120° C.,preferably between 50 and 110° C.

[0039] Per mol of (IV), from 1 to 1.5 equivalents of hydroxylamine(salt) are used, and from 100 to 3000 ml, preferably from 500 to 1500ml, of aqueous formic acid are used.

[0040] The starting materials can be added in different orders. Forexample, all of the starting materials can be initially introduced andthen heated up to the reaction temperature together. It is, however,also possible to initially introduce the hydroxylamine (salt) into theaqueous formic acid, and introduce the starting material (IV) at thereaction temperature.

[0041] Alternatively, the starting material (IV), which can also be usedmoistened with sulphuric acid, can be introduced into the aqueous formicacid, and the hydroxylamine (salt) or a solution of the hydroxylamine(salt) in water or aqueous formic acid can be metered in at the reactiontemperature.

[0042] For work-up, the mixture is further diluted With water, and (IX)is filtered off as solid.

[0043] 3-Cyano-2,4-dichloro-5-fluorobenzoic acid (IX) is converted intobenzoyl chloride (II) using a chlorinating agent as reagent.

[0044] Suitable chlorinating agents are those agents given below underthe reaction conditions stated there.

[0045] The preparation of 2,4-dichloro-3-cyano-5-fluoro-benzoyl chloride(II) by elimination of water from2,4-dichloro-5-fluoro-3-N-hydroxyiminomethyl-benzoic acid (III) withsimultaneous conversion of the carboxylic acid function into thecarbonyl chloride takes place using a chlorinating agent as reagent.

[0046] Suitable chlorinating agents are inorganic or organic acidchlorides, such as, for example, phosgene (carbonyl dichloride) or thesynthetic equivalents trichloromethyl chloroformate orbis(trichloromethyl) carbonate, oxalyl chloride, acetyl chloride,thionyl chloride, sulphuryl chloride, phosphorous trichloride,phosphorous pentachloride or phosphorous oxychloride and mixturesthereof. Preference is given to phosgene or thionyl chloride.

[0047] The reaction can be carried out in the presence or absence of asuitable diluent. Suitable diluents for this purpose are organicsolvents, an acid chloride which is liquid under the reactionconditions, i.e. the reagent itself, and any mixtures thereof. Examplesof organic solvents which may be mentioned are: aliphatic, alicyclic oraromatic hydrocarbons, such as, for example, petroleum ether, hexane,heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene ordecalin; halogenated hydrocarbons, such as, for example, chlorobenzene,dichlorobenzene, methylene chloride, chloroform, tetrachloromethane,dichloroethane, trichloroethane or tetrachloroethylene; ethers, such asdiethyl ether, diisopropyl ether, methyl t-butyl ether, methyl t-amylether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane,1,2-diethoxyethane, diethylene glycol dimethyl ether or anisole.

[0048] The oxime compound and chlorinating agent can be added in anyorder. In a preferred embodiment, the solvent-free reagent is initiallyintroduced, and 2,4-dichloro-5-fluoro-3-N-hydroxyiminomethyl-benzoicacid is metered in continuously or in portions at a rate of controllablegas evolution (hydrogen chloride and in some cases other gases such ascarbon dioxide or sulphur dioxide).

[0049] From 2 to 10 mol of acid chloride are generally used per mol ofcompound (III). It is also possible to use a larger excess, particularlywhen the acid chloride also serves as diluent.

[0050] The temperature in the reaction can be varied in a relativelywide range. It is generally chosen to be between 0 and 150° C.,preferably between 30° C. and boiling temperature. The process isgenerally carried out under atmospheric pressure. It is also possible tocarry out the reaction under reduced or elevated pressure. For example,when phosgene is used, it is wise to keep it liquid at a temperatureabove the boiling point at atmospheric pressure and to release the gaseswhich are liberated by means of a pressure-relief device.

[0051] The mixture can be worked up, for example, by fractionaldistillation.

[0052] The final fluorine/chlorine exchange takes place nucleophilicallyusing a fluoride source.

[0053] Suitable fluoride sources are, for example, metal fluorides,preferably alkali metal fluorides, such as, for example, potassiumfluoride or caesium fluoride.

[0054] The fluorination is carried out in the presence of a diluent.Suitable diluents are polar aprotic solvents such as, for example,amides, such as N,N-dimethylformamide, N,N-dimethylacetamide,N-methylformanilide, N-methylpyrrolidone or hexamethyl-phosphoramide;ureas, such as N,N-dimethylpropyleneurea, N,N-dimethyl-ethyleneurea;sulphoxides, such as dimethyl sulphoxide; sulphones, such as sulpholane.

[0055] The fluorination can also be carried out in the presence of knowncatalysts for halex reactions.

[0056] Per mol of 2,4-dichloro-3-cyano-5-fluoro-benzoyl chloride, from 3to 10 mol, preferably from 3.4 to 8 mol, particularly preferably from3.7 to 6 mol of fluoride are used.

[0057] The fluorination is carried out at elevated temperature. Thetemperature is generally from 100 to 250° C., preferably from 130 to200° C.

[0058] Work-up can, for example, involve distillation of the productunder reduced pressure, or extraction using a solvent and subsequentfractional distillation.

[0059] The preparation of 3-cyano-2,4,5-trifluoro-benzoyl chloride from3-cyano-2,4,5-trifluoro-benzoyl fluoride (I) according to the inventionis carried out analogously to known processes for the rechlorination ofcarbonyt fluorides. Reagents which are suitable for this purpose aresilicon chlorides, such as, for example, silicon tetrachloride,trimethylchlorosilane or dimethyldichlorosilane; or calcium chloride, ineach case in the presence of catalytic amounts of a Lewis acid, such as,for example, aluminium chloride or boron trichloride; or said or otherchlorine-containing Lewis acids themselves.

[0060] Per mol of compound (I), from 1 to 2 equivalents of reagent and,where appropriate, from 0.01 to 0.1 mol of Lewis acid are generallyused.

[0061] The temperature in the reaction can be varied within a relativelywide range. The reaction is generally carried out at from 20 to 150° C.when silicon chlorides and Lewis acids are used, and at from 120 to 200°C. when calcium chloride is used.

[0062] Work-up is preferably by vacuum distillation.

[0063] It is extremely surprising that the ring chlorination of5-fluoro-1,3-xylene to give 2,4-dichloro-5-fluoro-1,3-dimethylbenzeneproceeds with very high selectivity, without which the synthesissequence according to the invention would not be possible.

[0064] Further details of the processes are given in the examples below,without the invention being limited thereby.

EXAMPLE 1

[0065] Preparation of 2,4-dichloro-5-fluoro-1,3-dimethylbenzene

[0066] a) solvent-free

[0067] 1 g of anhydrous iron(III) chloride were introduced into 124 g of3,5-dimethyl-fluorobenzene, and chlorine was introduced at the rate ofthe reaction (about 4 h). The reaction is initially slightly exothermic(temperature increase from 24 to 320° C.) and was maintained below 30°C. by gentle cooling. After 120 g of chlorine had been introduced, themixture solidified. According to GC analysis, 33.4% of monochlorinatedcompound, 58.4% of desired product and 5% of superchlorinated compoundshad formed. After the hydrogen chloride had been stripped off,distillation was carried out in a water-jet vacuum on a column.

[0068] In the initial fraction, at 72-74° C./22 mbar, 49 g of2-chloro-5-fluoro-1,3-dimethyl-benzene were obtained. After anintermediate fraction of 5 g, at 105° C./22 mbar, 75 g of2,4-dichloro-5-fluoro- 1,3-dimethylbenzene passed over. Melting range:64-65° C.

[0069] b) in 1,2-dichloroethane

[0070] 1 kg of 3,5-dimethyl-fluorobenzene and 15 g of anhydrousiron(III) chloride were introduced into 1 l of 1,2-dichloroethane, andchlorine was introduced at the rate of the reaction (about 4 h). Thereaction is initially slightly exothermic (temperature increase from 24to 32° C.) and was maintained below 30° C. by gentle cooling. After 1200g of chlorine had been absorbed, according to GC analysis, 4% ofmonochlorinated compound, 81.1% of desired product and 13.3% ofsuperchlorinated compounds had formed. After the solvent and hydrogenchloride had been distilled off, distillation was carried out in awater-jet vacuum on a column.

[0071] In the initial fraction, 40 g of2-chloro-5-fluoro-1,3-dimethylbenzene were obtained. After a smallintermediate fraction, 1115 g of2,4-dichloro-5-fluoro-1,3-dimethylbenzene passed over at 127-128° C./50mbar.

EXAMPLE 2

[0072] 2,4-Dichloro-5-fluoro-3-dichloromethyl-1-trichloromethylbenzene

[0073] 1890 g of 2,4-dichloro-5-fluoro-1,3-dimethylbenzene wereintroduced into a photochlorination apparatus with chlorine inlet andoutlet for the hydrogen chloride to a scrubber and a light source in thevicinity of the chlorine inlet pipe, and chlorine was metered in at from140 to 150° C. After 30 h, 3850 g of chlorine had been introduced. Thecontent of desired product was 71.1% according to GC analysis; theproportion of insufficiently chlorinated compounds was 27.7%.

[0074] Distillation over a 60 cm column containing Wilson spiral gave aninitial fraction of 1142 g, which could be reintroduced into thechlorination. The main fraction at 160-168° C./0,2 mbar gave 2200 g of2,4-dichloro-5-fluoro-3-dichloromethyl-1-trichloro-methylbenzene havinga melting range of 74-76° C.

[0075] After recrystallization of a sample from methanol, the meltingpoint was 81-82° C. The initial fraction from this reaction can bereintroduced into the chlorination with new starting material (1555 g).This gave 1377 g of initial fraction and 2465 g of main fraction with apurity of 97.4%.

EXAMPLE 3

[0076]2,4-Dichloro-5-fluoro-3-formyl-benzoic acid

[0077] At 70° C., 2500 ml of 95% strength sulphuric acid were initiallyintroduced into a stirred apparatus fitted with a gas outlet, and 500 gof molten2,4-dichloro-5-fluoro-3-dichloromethyl-1-trichloromethylbenzene wereadded dropwise with stirring. After a short while, evolution of hydrogenchloride commenced. After 2 h everything had been metered in andstirring was continued until the evolution of gas ceased. After thereaction mixture had cooled to 20° C., it was discharged onto 4 kg ofice, and the precipitated solid was filtered off with suction. Theproduct was then washed with water and dried. The yield of2,4-dichloro-5-fluoro-3-formyl-benzoic acid was 310 g. Melting range:172-174° C.

[0078] Repetition of the experiment using 2390 g of starting material,7170 ml of sulphuric acid gave 1540 g of product (97.8% purity).

EXAMPLE 4

[0079]2,4-Dichloro-5-fluoro-3-N-hydroxyiminomethyl-benzoic acid

[0080] 80 g of hydroxylammonium chloride in 500 ml of ethanol wereintroduced into a stirred apparatus, and 200 ml of 45% strength sodiumhydroxide solution were added dropwise, and 200 g of2,4-dichloro-5-fluoro-3-formyl-benzoic acid were then introduced at40-45° C. The reaction was slightly exothermic and stirring wascontinued for 5 h at 60° C. After the mixture had been cooled to roomtemperature, the pH was adjusted to <3 by the dropwise addition ofhydrochloric acid. The product was taken up in tert-butyl methyl ether,and the organic phase was separated off. The solvent was distilled offto leave 185 g of 2,4-dichloro-5-fluoro-3-N-hydroxyiminomethyl-benzoicacid. Melting range: 190-194° C.

[0081] Repetition of this example in water instead of ethanol using 60.5g of hydroxyl-ammonium chloride in 363 ml of water, 150 ml of 45% NaOH,150 g of starting material gave 150 g of product (93.4% purity).

EXAMPLE 5

[0082]2,4-Dichloro-3-cyano-5-fluoro-benzoylchloride

[0083] 600 ml of thionyl chloride were introduced into a stirredapparatus fitted with a metering device and a gas outlet leading to ascrubber via a reflux condenser, and, at 20° C., 210 g of startingmaterial were introduced at the rate of hydrogen chloride/sulphurdioxide evolution. At the end of the addition, the mixture was heated toreflux until the evolution of gas ceased. The mixture was thendistilled. In the boiling range from 142-145° C./10 mbar, 149 g of2,4-dichloro-3-cyano-5-fluoro-benzoylchloride were obtained (contentaccording to GC: 98,1%). Melting range: 73-75° C.

[0084] Repetition of this example using 450 g of phosphorous oxychloridein 200 ml of chlorobenzene as chlorinating agent gave, from 80 g ofstarting material (80%), 48 g of product (89.0% purity).

EXAMPLE 6

[0085] 3-Cyano-2,4,5-trifluoro-benzoyl fluoride

[0086] 50 g of potassium fluoride were suspended in 120 ml oftetramethylene sulphone, and the suspension is dried by gentlydistilling it at 15 mbar (about 20 ml). 50.4 g of2,4-dichloro-3-cyano-5-fluoro-benzoyl chloride were then added, and themixture was stirred with the exclusion of moisture at an internaltemperature of 180° C. for 12 hours. Vacuum distillation gave 32.9 g of3-cyano-2,4,5-trifluoro-benzoyl fluoride in the boiling range from98-100° C./12 mbar.

EXAMPLE 7

[0087] 3-Cyano-2,4,5-trifluoro-benzoyl chloride

[0088] 76.6 g of 3-cyano-2,4,5-trifluoro-benzoyl fluoride were initiallyintroduced together with 1 g of anhydrous aluminium chloride at 60-65°C., and 25 g of silicon tetrachloride were then added dropwise at therate of gas evolution. After the evolution of gas at 65° C. had ceased,the mixture was distilled under reduced pressure. In the boiling rangefrom 120-122° C./14 mbar, 73.2 g of 3-cyano-2,4,5-trifluoro-benzoylchloride passed over.

EXAMPLE 8

[0089]3Cyano-2,4-dichloro-5-fluorobenzoic acid

[0090] 162 g of hydroxylamine hydrochloride were introduced into 2000 mlof formic acid (technical-grade, 85% strength). At 95° C., 950 g of2,4-dichloro-5-fluoro-3-formylbenzoic acid (moistened with sulphuricacid, 42% strength) were introduced. As a result, the mixture foamedbriefly and then a clear solution was immediately obtained. The mixturewas then stirred for 4 hours at from 100 to 105° C. (reflux).

[0091] After the mixture had been cooled to room temperature, it waspoured onto water, thoroughly stirred, filtered with suction and dried.This gave 364 g (90.3% of theory) of3-cyano-2,4-dichloro-5-fluorobenzoic acid with a content, according toGC, of 97.7%.

EXAMPLE 9

[0092]3-Cyano-2,4-dichloro-5-fluorobenzoyl chloride

[0093] 4100 ml of thionyl chloride and 41 ml of pyridine were introducedinto a stirred apparatus fitted with metering device and gas outletleading to a scrubber via a reflux condenser, and, at 20° C., 2050 g of3-cyano-2,4-dichloro-5-fluorobenzoic acid (99.5% strength) wereintroduced at the rate of hydrogen chloride/sulphur dioxide evolution.At the end of the addition, the mixture was heated to reflux until theevolution of gas ceased. The mixture was then distilled. In the boilingrange from 142 to 145° C./10 mbar, 2150 g (95.7% of theory) of3-cyano-2,4-dichloro-5-fluorobenzoyl chloride were obtained (contentaccording to GC: 98.0%).

1. 3-Cyano-2,4,5-trifluoro-benzoyl fluoride of the formula (I)


2. Process for the preparation of 3-cyano-2,4,5-trifluoro-benzoyl fluoride of the formula (I) according to claim 1, characterized in that 3-cyano-2,4-dichloro-5-fluoro-benzoyl chloride is reacted nucleophilically with a fluoridizing agent according to the following equation:


3. Use of 3-cyano-2,4,5-trifluoro-benzoyl fluoride for the preparation of 3-cyano-2,4,5-trifluoro-benzoyl chloride by reaction of 3-cyano-2,4,5-trifluoro-benzoyl fluoride with chlorinating agents, optionally in the presence of diluents.
 4. Process for the preparation of 2,4-dichloro-3-cyano-5-fluoro-benzoyl chloride of the formula (II) by elimination of water from 2,4-dichloro-5-fluoro-3-N-hydroxyiminomethyl-benzoic acid (III) with simultaneous conversion of the carboxylic acid function into the carbonyl chloride according to the following equation:


5. 2,4-Dichloro-5-fluoro-3-N-hydroxyimino-methyl-benzoic acid of the formula (III)


6. Process for the preparation of 2,4-dichloro-5-fluoro-3-N-hydroxylminomethyl-benzoic acid of the formula (III) according to claim 5, by reaction of 2,4-dichloro-5-fluoro-3-formyl-benzoic acid of the formula (IV) with hydroxylamine according to the following equation.


7. Process for the preparation of 2,4-dichloro-3-cyano-5-fluoro-benzoic acid a) by elimination of water from 2,4-dichloro-5fluoro-3-N-hydroxyiminomethyl-benzoic acid of the formula (III) according to the following equation

 b) by reaction of 2,4-dichloro-5-fluoro-3-formyl-benzoic acid of the formula (IV) with hydroxylamine in the presence of formic acid according to the following equation


8. 2,4-Dichloro-5-fluoro-3-formyl-benzoic acid of the formula (IV)


9. Process for the preparation of 2,4-dichloro-5-fluoro-3-formyl-benzoic acid of the formula (IV) according to claim 7,

 a) by hydrolysis of 2,4-dichloro-5-fluoro-3-dichloromethyl-benzoic acid or b) by hydrolysis of 2,4-dichloro-5-fluoro-3-dichloromethyl-1-trichloro-methylbenzene of the formula (VI), in each case in the presence of acids and optionally in protic solvents.
 10. 2,4-dichloro-5-fluoro-3-dichloromethyl-1-trichloromethylbenzene of the formula (VI)


11. Process for the preparation of 2,4-dichloro-5-fluoro-3-dichloromethyl-1-trichloromethylbenzene of the formula (VI),

 according to claim 10 by side-chain chlorination of 2,4-dichloro-5-fluoro-1,3-dimethylbenzene (VII) to give 2,4-dichloro-5-fluoro-3-dichloromethyl-1-trichloromethylbenzene (VI) according to the following equation:

 characterized in that the chlorination is carried out under free-radical conditions and/or at elevated temperature.
 12. 2,4-dichloro-5-fluoro-1,3-dimethylbenzene of the formula (VII)


13. Process for the preparation of 2,4-dichloro-5-fluoro-1,3-dimethylbenzene of the formula (VII) according to claim 12 by ring chlorination of 5-fluoro-1,3-xylene (VIII) to give 2,4-dichloro-5-fluoro-1,3-dimethylbenzene (VII) using chlorine gas, optionally in a diluent and in the presence of a catalyst according to the following equation: 